Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma

OBJECTIVES: * Determine the feasibility of expanding ex vivo autologous T cells and infusing these cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in patients with multiple myeloma. * Determine the response rate and progression-free survival of patients who receive anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100 post-transplantation. * Compare response and survival rates of these patients to historical controls. * Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an anti-pneumococcal immune response post-transplantation in these patients. * Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem cell graft results in an earlier and/or enhanced immune response than with a graft containing "non-educated" APCs in these patients. * Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo contributes to the anti-pneumococcal immune response in these patients. OUTLINE: This is a randomized, multicenter study. Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells. Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1 only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover. Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4 treatment arms. * Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs IV over 20-60 minutes around day 12-14 post-transplantation. * Arm II: Patients receive PCV as in arm I but receive ATCs around day 100 post-transplantation. * Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as in arm I. * Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation. All patients are offered standard pneumococcal polysaccharide vaccine at 12 months. Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months, and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.